Management of hyperthyroidism in pregnancy

Hyperthyroidism in pregnancy is associated with adverse foetal, maternal and obstetrical outcome. Untreated or inadequately treated hyperthyroidism may precipitate pre eclampsia and congestive cardiac failure in mother. It also increases the risk of miscarriage, abruption placentae and premature delivery in such patients. Maintaining euthyroidism in these patients is of utmost importance. Antithyroid medications are used as first line treatment for such patients to restore euthyroid status at the earliest. Radioactive iodine is absolutely contraindicated in pregnancy and surgery often requires pre-treatment with anti thyroid medications. Two drugs are available –carbimazole and propylthiouracil. Use of carbimazole/methimazole in pregnancy is not only associated with increased incidence of scalp defect(aplasia cutis ) in the infants, but some specific congenital malformation like choanal atresia, oesophageal atresia, trachea-oesophageal fistula, patent vitello intestinal duct, omphalocele, dysmorphic facial features and growth retardation do occur. These malformations represent carbimazole /methimazole embryopathy. Due to the association of foetal teratogenicity with carbimazole /methimazole, propylthiouracil is recommended as the drug of choice in first trimester of pregnancy. However, as its use is associated with risk of hepatotoxicity, it should be changed to carbimazole/methimazole thereafter

Thyrotoxic periodic paralysis: a short clinical review

Thyrotoxic Periodic Paralysis (TPP) is a potentially lethal manifestation of hyperthyroidism which is characterized by hypokalemia and muscular weakness. It mainly affects Asian men in the age group of 20 to 40 years. Immediate supplementation with oral or intravenous potassium will help to not only abort the acute attack of paralysis but will also prevent serious and life threatening cardiac arrhythmias. Non selective beta blockers like propranolol can also be used to ameliorate and prevent subsequent paralytic attack. Acetazolamide has no role in the treatment of TPP

Managing paediatric Graves’ disease

Graves’ disease is the most common cause of hyperthyroidism in children. Anti-thyroid drug treatment with carbimazole or its active metabolite methimazole is offered as first line initial treatment but it induces remission in only 30%of children. Propylthiouracil is not recommended in children because of its association with severe hepatic toxicity. For those who relapse after ATD, radioactive iodine can be offered as definitive therapy except in cases with severe Graves’ ophthalmopathy or patients with large goitre who are the candidates for surgery. Total (or near total) thyroidectomy  is the surgical procedure of choice for treating paediatric patients with  Graves’ disease as it reduces the risk of recurrent hyperthyroidism which was seen in patients undergoing subtotal or partial thyroidectomy

Gardner's syndrome in a 40-year-old woman: successful treatment of locally aggressive desmoid tumors with cytotoxic chemotherapy

BACKGROUND: Desmoid tumors that present as a part of Gardener's syndrome can present very difficult management problems. CASE PRESETATION: We report a case of intra-abdominal desmoid tumor causing distal small bowel obstruction that complicated the management of a more proximal enterocutaneous fistula from the jejunum. After failure of more conventional management options including imatinib, the patient's disease responded to doxorubicin and ifosfamide. The response resolved the bowel obstruction and allowed small intestinal resection to resolve the enterocutaneous fistula. CONCLUSION: Systemic cytotoxic therapy with doxorubicin and ifosfamide can be useful for patients with complications from intra-abdominal desmoid tumor

Chordoma: The Nonsarcoma Primary Bone Tumor

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139965/1/onco1344.pd

Epidermal Growth Factor Receptor Expression and Mutational Analysis in Synovial Sarcomas and Malignant Peripheral Nerve Sheath Tumors

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140003/1/onco0459.pd

Primary Cardiac Sarcoma: A Rare, Aggressive Malignancy with a High Propensity for Brain Metastases.

Introduction: Primary cardiac sarcoma (PCS) has a poor prognosis compared to other sarcomas due to late presentation, challenging resection, incidence of metastases, and limited efficacy of systemic therapies. Methods: A medical record search engine was queried to identify patients diagnosed with PCS from 1992 to 2017 at the University of Michigan. Results: Thirty-nine patients with PCS had a median age of 41 years (range 2-77). Common histologies were angiosarcoma (AS, 14), high-grade undifferentiated pleomorphic sarcoma (UPS, 10), and leiomyosarcoma (LMS, 5). Sites of origin were left atrium (18), right atrium (16), and pericardium (5). AS was the most common right-sided tumor; UPS was more common on the left. Eighteen patients presented with metastases involving lung (10), bone (7), liver (5), and brain (4). Twenty-five patients underwent resection, achieving 3 R Conclusions: PCS portends a poor prognosis, because of difficulty in obtaining complete resection of sarcoma, advanced stage at diagnosis, and high risk of brain metastases. Providers should be aware of the increased risk of brain metastases and consider brain imaging at diagnosis and follow-up

Psychosocial, behavioral, and supportive interventions for pediatric, adolescent, and young adult cancer survivors: a systematic review and meta-analysis

Background Pediatric, adolescent, and young adult (PAYA) cancer survivors suffer from multiple domains of adverse psychosocial and behavioral outcomes during and after their cancer treatment. This study conducted a systematic review and metaanalysis of psychosocial, behavioral, and supportive interventions for PAYA cancer survivors. Methods We searched 11 electronic databases, 4 professional websites, and manual search of reference lists in existing reviews. We selected randomized controlled trials and controlled trials without randomization focusing on PAYA cancer survivors across six outcome domains. Results We included 61 studies (4,402 participants) published between 1987 and 2020. Overall risk of bias across studies was low. We identified an overall moderate and statistically significant treatment effect size for PAYA cancer survivors across six outcome domains. Conclusion psychosocial, behavioral, and supportive interventions were overall effective for PAYA cancer survivors. However, interventions were not effective for certain outcome domains, and less effective among AYA versus pediatric cancer survivors.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/167608/1/Zhang_et al. CROH.pdfDescription of Zhang_et al. CROH.pdf : Main articleSEL

Phase II Study of Sequential Gemcitabine Followed by Docetaxel for Recurrent Ewing Sarcoma, Osteosarcoma, or Unresectable or Locally Recurrent Chondrosarcoma: Results of Sarcoma Alliance for Research Through Collaboration Study 003

Background.Gemcitabine and docetaxel have a broad spectrum of clinical activity in patients with carcinoma. The Sarcoma Alliance for Research Through Collaboration conducted a phase II trial of gemcitabine in combination with docetaxel in children and adults with recurrent Ewing sarcoma (EWS), osteosarcoma (OS), or unresectable or recurrent chondrosarcoma. The primary objective was to determine the objective response rate using Response Evaluation Criteria in Solid Tumors (RECIST).Methods.Gemcitabine (675 mg/m2 i.v. over 90 minutes on days 1 and 8) was administered in combination with docetaxel (75 mg/m2 i.v. over 1 hour on day 8) every 21 days. All patients received filgrastim or pegfilgrastim. A Bayesian formulation was used to determine the probability of achieving the target response rate for each subtype—0.35 for EWS and OS or 0.20 for chondrosarcoma. If the probability of achieving the target response rate was <0.05, the combination was considered inactive. Toxicity was graded according to Common Terminology Criteria for Adverse Events (CTCAE), version 3.0.Results.Fifty‐three eligible patients were enrolled in the three subtype groups—OS (n = 14), EWS (n = 14), and chondrosarcoma (n = 25). Toxicities included neutropenia, thrombocytopenia, fatigue, dyspnea, bronchospasm, edema, neuropathy, and liver function abnormalities. Dose modification for toxicity was required for eight patients during cycle 1 and 16 patients in subsequent cycles. Seven patients withdrew from therapy as a result of toxicity. No complete responses were observed. Partial responses were observed in OS (n = 1), EWS (n = 2), and chondrosarcoma (n = 2) patients.Conclusion.Gemcitabine in combination with docetaxel was associated with a probability of reaching the target 35% response rate of <5% in OS patients and 5.6% in EWS patients; the probability of reaching a 20% response rate in chondrosarcoma patients was 14%.摘要背景. 吉西他滨与多西他赛对癌症患者有广谱的临床疗效。 肉瘤研究联盟协作组在复发的尤文肉瘤 （EWS）、 骨肉瘤 （OS）、 不可切除或复发的软骨肉瘤成人和儿童患者中开展了吉西他滨联合多西他赛的 II 期试验。 主要目的为通过实体瘤疗效评估标准 （RECIST） 确定客观缓解率。方法. 吉西他滨 （675 mg/m2， 静脉滴注 90 分钟以上， 第 1 和 8 天） 联合多西他赛 （75 mg/m2， 静脉滴注 1 小时以上， 第 8 天） 每 21 天给药 1 次。 全部患者均同时接受非格司亭或乙二醇化非格司亭。 利用贝叶斯公式来确定各个亚型达到目标缓解率的概率——EWS 和 OS 为 0.35， 软骨肉瘤为 0.20。 如果达到目标缓解率的概率 < 0.05， 则认为联合方案无效。 毒性反应根据不良事件通用术语标准 （CTCAE） 3.0 版来分级。结果. 53 例合格患者入组 3 个亚型组 ： OS （n=14）、 EWS （n=14）、 软骨肉瘤 （n=25）。 毒性反应包括中性粒细胞减少、 血小板减少、 乏力、 呼吸困难、 支气管痉挛、 水肿、 神经病变以及肝功能异常。 第 1 个周期有 8 例患者、 其后周期有 16 例患者因毒性反应而需要剂量调整。 7 例患者因毒性反应而撤出治疗。 未观察到完全缓解。 OS （n=1）、 EWS （n=2） 和软骨肉瘤 （n=2） 组均有患者达到部分缓解。结论. 吉西他滨联合多西他赛在 < 5% 的 OS 患者、 5.6% 的 EWS 患者中达到目标缓解率的概率为 35%； 14% 软骨肉瘤患者中达到目标缓解率的概率为 20%。讨论. 贝叶斯公式能够评估各个亚型在分别进行缓解率评估后预测达到目标缓解率的概率。 通过多角度来看这些数据， 在考量达到目标缓解率的概率以及入组率之后即能发现本研究设计方案阻碍了研究的继续开展。 因为这一设计方案并未设定判断治疗为 “有效” 的规则， 所以并不适合与标准的分 2 阶段进行的 II 期试验设计直接比较。 关闭 EWS 和软骨肉瘤亚组的决定， 某种程度上是基于入组缓慢， 另外达到目标缓解率的概率较低也支持这一决定。 入组率而不是统计设计， 对试验周期有显著影响。The Oncologist 2012;17:321‐e329Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139909/1/onco0321-sup-0002.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139909/2/onco0321-sup-0001.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139909/3/onco0321.pd